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Research ArticleSpecial Issue IUPHAR Compendium of the Pharmacology and Classification of the Nuclear Receptor Superfamily 2006

International Union of Pharmacology. LXVI. Orphan Nuclear Receptors

Gérard Benoit, Austin Cooney, Vincent Giguere, Holly Ingraham, Mitch Lazar, George Muscat, Thomas Perlmann, Jean-Paul Renaud, John Schwabe, Frances Sladek, Ming-Jer Tsai and Vincent Laudet
Pharmacological Reviews December 2006, 58 (4) 798-836; DOI: https://doi.org/10.1124/pr.58.4.10
Gérard Benoit
Structure and Evolution of Nuclear Hormone Receptors, Unité Mixte de Recherche 5161 du Centre National de la Recherche Scientifique, Institut National de la Recherche Agronomique 1237, Laboratoire de Biologie Moléculaire de la Cellule, Institut Fédératif de Recherche 128 BioSciences Lyon-Gerland, Ecole Normale Supérieure de Lyon, Lyon, France (G.B., V.L.); Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, Texas (A.C., M.-J.T.); Molecular Oncology Group, McGill University Health Centre, Montréal, Québec, Canada (V.G.); Department of Physiology, University of California, San Francisco, San Francisco, California (H.I.); Division of Endocrinology, Diabetes, and Metabolism, Institute for Diabetes, Obesity, and Metabolism, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania (M.L.); Institute for Molecular Bioscience, The University of Queensland, St. Lucia, Queensland, Australia (G.M.); Ludwig Institute for Cancer Research, Department of Cell and Molecular Biology, Karolinska Institutet, Stockholm, Sweden (T.P.); AliX, Illkirch, France (J.-P.R.); Medical Research Council Laboratory of Molecular Biology, Cambridge, United Kingdom (J.S.); and Department of Cell Biology and Neuroscience, University of California, Riverside, California (F.S.)
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Austin Cooney
Structure and Evolution of Nuclear Hormone Receptors, Unité Mixte de Recherche 5161 du Centre National de la Recherche Scientifique, Institut National de la Recherche Agronomique 1237, Laboratoire de Biologie Moléculaire de la Cellule, Institut Fédératif de Recherche 128 BioSciences Lyon-Gerland, Ecole Normale Supérieure de Lyon, Lyon, France (G.B., V.L.); Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, Texas (A.C., M.-J.T.); Molecular Oncology Group, McGill University Health Centre, Montréal, Québec, Canada (V.G.); Department of Physiology, University of California, San Francisco, San Francisco, California (H.I.); Division of Endocrinology, Diabetes, and Metabolism, Institute for Diabetes, Obesity, and Metabolism, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania (M.L.); Institute for Molecular Bioscience, The University of Queensland, St. Lucia, Queensland, Australia (G.M.); Ludwig Institute for Cancer Research, Department of Cell and Molecular Biology, Karolinska Institutet, Stockholm, Sweden (T.P.); AliX, Illkirch, France (J.-P.R.); Medical Research Council Laboratory of Molecular Biology, Cambridge, United Kingdom (J.S.); and Department of Cell Biology and Neuroscience, University of California, Riverside, California (F.S.)
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Vincent Giguere
Structure and Evolution of Nuclear Hormone Receptors, Unité Mixte de Recherche 5161 du Centre National de la Recherche Scientifique, Institut National de la Recherche Agronomique 1237, Laboratoire de Biologie Moléculaire de la Cellule, Institut Fédératif de Recherche 128 BioSciences Lyon-Gerland, Ecole Normale Supérieure de Lyon, Lyon, France (G.B., V.L.); Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, Texas (A.C., M.-J.T.); Molecular Oncology Group, McGill University Health Centre, Montréal, Québec, Canada (V.G.); Department of Physiology, University of California, San Francisco, San Francisco, California (H.I.); Division of Endocrinology, Diabetes, and Metabolism, Institute for Diabetes, Obesity, and Metabolism, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania (M.L.); Institute for Molecular Bioscience, The University of Queensland, St. Lucia, Queensland, Australia (G.M.); Ludwig Institute for Cancer Research, Department of Cell and Molecular Biology, Karolinska Institutet, Stockholm, Sweden (T.P.); AliX, Illkirch, France (J.-P.R.); Medical Research Council Laboratory of Molecular Biology, Cambridge, United Kingdom (J.S.); and Department of Cell Biology and Neuroscience, University of California, Riverside, California (F.S.)
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Holly Ingraham
Structure and Evolution of Nuclear Hormone Receptors, Unité Mixte de Recherche 5161 du Centre National de la Recherche Scientifique, Institut National de la Recherche Agronomique 1237, Laboratoire de Biologie Moléculaire de la Cellule, Institut Fédératif de Recherche 128 BioSciences Lyon-Gerland, Ecole Normale Supérieure de Lyon, Lyon, France (G.B., V.L.); Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, Texas (A.C., M.-J.T.); Molecular Oncology Group, McGill University Health Centre, Montréal, Québec, Canada (V.G.); Department of Physiology, University of California, San Francisco, San Francisco, California (H.I.); Division of Endocrinology, Diabetes, and Metabolism, Institute for Diabetes, Obesity, and Metabolism, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania (M.L.); Institute for Molecular Bioscience, The University of Queensland, St. Lucia, Queensland, Australia (G.M.); Ludwig Institute for Cancer Research, Department of Cell and Molecular Biology, Karolinska Institutet, Stockholm, Sweden (T.P.); AliX, Illkirch, France (J.-P.R.); Medical Research Council Laboratory of Molecular Biology, Cambridge, United Kingdom (J.S.); and Department of Cell Biology and Neuroscience, University of California, Riverside, California (F.S.)
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Mitch Lazar
Structure and Evolution of Nuclear Hormone Receptors, Unité Mixte de Recherche 5161 du Centre National de la Recherche Scientifique, Institut National de la Recherche Agronomique 1237, Laboratoire de Biologie Moléculaire de la Cellule, Institut Fédératif de Recherche 128 BioSciences Lyon-Gerland, Ecole Normale Supérieure de Lyon, Lyon, France (G.B., V.L.); Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, Texas (A.C., M.-J.T.); Molecular Oncology Group, McGill University Health Centre, Montréal, Québec, Canada (V.G.); Department of Physiology, University of California, San Francisco, San Francisco, California (H.I.); Division of Endocrinology, Diabetes, and Metabolism, Institute for Diabetes, Obesity, and Metabolism, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania (M.L.); Institute for Molecular Bioscience, The University of Queensland, St. Lucia, Queensland, Australia (G.M.); Ludwig Institute for Cancer Research, Department of Cell and Molecular Biology, Karolinska Institutet, Stockholm, Sweden (T.P.); AliX, Illkirch, France (J.-P.R.); Medical Research Council Laboratory of Molecular Biology, Cambridge, United Kingdom (J.S.); and Department of Cell Biology and Neuroscience, University of California, Riverside, California (F.S.)
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George Muscat
Structure and Evolution of Nuclear Hormone Receptors, Unité Mixte de Recherche 5161 du Centre National de la Recherche Scientifique, Institut National de la Recherche Agronomique 1237, Laboratoire de Biologie Moléculaire de la Cellule, Institut Fédératif de Recherche 128 BioSciences Lyon-Gerland, Ecole Normale Supérieure de Lyon, Lyon, France (G.B., V.L.); Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, Texas (A.C., M.-J.T.); Molecular Oncology Group, McGill University Health Centre, Montréal, Québec, Canada (V.G.); Department of Physiology, University of California, San Francisco, San Francisco, California (H.I.); Division of Endocrinology, Diabetes, and Metabolism, Institute for Diabetes, Obesity, and Metabolism, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania (M.L.); Institute for Molecular Bioscience, The University of Queensland, St. Lucia, Queensland, Australia (G.M.); Ludwig Institute for Cancer Research, Department of Cell and Molecular Biology, Karolinska Institutet, Stockholm, Sweden (T.P.); AliX, Illkirch, France (J.-P.R.); Medical Research Council Laboratory of Molecular Biology, Cambridge, United Kingdom (J.S.); and Department of Cell Biology and Neuroscience, University of California, Riverside, California (F.S.)
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Thomas Perlmann
Structure and Evolution of Nuclear Hormone Receptors, Unité Mixte de Recherche 5161 du Centre National de la Recherche Scientifique, Institut National de la Recherche Agronomique 1237, Laboratoire de Biologie Moléculaire de la Cellule, Institut Fédératif de Recherche 128 BioSciences Lyon-Gerland, Ecole Normale Supérieure de Lyon, Lyon, France (G.B., V.L.); Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, Texas (A.C., M.-J.T.); Molecular Oncology Group, McGill University Health Centre, Montréal, Québec, Canada (V.G.); Department of Physiology, University of California, San Francisco, San Francisco, California (H.I.); Division of Endocrinology, Diabetes, and Metabolism, Institute for Diabetes, Obesity, and Metabolism, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania (M.L.); Institute for Molecular Bioscience, The University of Queensland, St. Lucia, Queensland, Australia (G.M.); Ludwig Institute for Cancer Research, Department of Cell and Molecular Biology, Karolinska Institutet, Stockholm, Sweden (T.P.); AliX, Illkirch, France (J.-P.R.); Medical Research Council Laboratory of Molecular Biology, Cambridge, United Kingdom (J.S.); and Department of Cell Biology and Neuroscience, University of California, Riverside, California (F.S.)
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Jean-Paul Renaud
Structure and Evolution of Nuclear Hormone Receptors, Unité Mixte de Recherche 5161 du Centre National de la Recherche Scientifique, Institut National de la Recherche Agronomique 1237, Laboratoire de Biologie Moléculaire de la Cellule, Institut Fédératif de Recherche 128 BioSciences Lyon-Gerland, Ecole Normale Supérieure de Lyon, Lyon, France (G.B., V.L.); Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, Texas (A.C., M.-J.T.); Molecular Oncology Group, McGill University Health Centre, Montréal, Québec, Canada (V.G.); Department of Physiology, University of California, San Francisco, San Francisco, California (H.I.); Division of Endocrinology, Diabetes, and Metabolism, Institute for Diabetes, Obesity, and Metabolism, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania (M.L.); Institute for Molecular Bioscience, The University of Queensland, St. Lucia, Queensland, Australia (G.M.); Ludwig Institute for Cancer Research, Department of Cell and Molecular Biology, Karolinska Institutet, Stockholm, Sweden (T.P.); AliX, Illkirch, France (J.-P.R.); Medical Research Council Laboratory of Molecular Biology, Cambridge, United Kingdom (J.S.); and Department of Cell Biology and Neuroscience, University of California, Riverside, California (F.S.)
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John Schwabe
Structure and Evolution of Nuclear Hormone Receptors, Unité Mixte de Recherche 5161 du Centre National de la Recherche Scientifique, Institut National de la Recherche Agronomique 1237, Laboratoire de Biologie Moléculaire de la Cellule, Institut Fédératif de Recherche 128 BioSciences Lyon-Gerland, Ecole Normale Supérieure de Lyon, Lyon, France (G.B., V.L.); Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, Texas (A.C., M.-J.T.); Molecular Oncology Group, McGill University Health Centre, Montréal, Québec, Canada (V.G.); Department of Physiology, University of California, San Francisco, San Francisco, California (H.I.); Division of Endocrinology, Diabetes, and Metabolism, Institute for Diabetes, Obesity, and Metabolism, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania (M.L.); Institute for Molecular Bioscience, The University of Queensland, St. Lucia, Queensland, Australia (G.M.); Ludwig Institute for Cancer Research, Department of Cell and Molecular Biology, Karolinska Institutet, Stockholm, Sweden (T.P.); AliX, Illkirch, France (J.-P.R.); Medical Research Council Laboratory of Molecular Biology, Cambridge, United Kingdom (J.S.); and Department of Cell Biology and Neuroscience, University of California, Riverside, California (F.S.)
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Frances Sladek
Structure and Evolution of Nuclear Hormone Receptors, Unité Mixte de Recherche 5161 du Centre National de la Recherche Scientifique, Institut National de la Recherche Agronomique 1237, Laboratoire de Biologie Moléculaire de la Cellule, Institut Fédératif de Recherche 128 BioSciences Lyon-Gerland, Ecole Normale Supérieure de Lyon, Lyon, France (G.B., V.L.); Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, Texas (A.C., M.-J.T.); Molecular Oncology Group, McGill University Health Centre, Montréal, Québec, Canada (V.G.); Department of Physiology, University of California, San Francisco, San Francisco, California (H.I.); Division of Endocrinology, Diabetes, and Metabolism, Institute for Diabetes, Obesity, and Metabolism, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania (M.L.); Institute for Molecular Bioscience, The University of Queensland, St. Lucia, Queensland, Australia (G.M.); Ludwig Institute for Cancer Research, Department of Cell and Molecular Biology, Karolinska Institutet, Stockholm, Sweden (T.P.); AliX, Illkirch, France (J.-P.R.); Medical Research Council Laboratory of Molecular Biology, Cambridge, United Kingdom (J.S.); and Department of Cell Biology and Neuroscience, University of California, Riverside, California (F.S.)
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Ming-Jer Tsai
Structure and Evolution of Nuclear Hormone Receptors, Unité Mixte de Recherche 5161 du Centre National de la Recherche Scientifique, Institut National de la Recherche Agronomique 1237, Laboratoire de Biologie Moléculaire de la Cellule, Institut Fédératif de Recherche 128 BioSciences Lyon-Gerland, Ecole Normale Supérieure de Lyon, Lyon, France (G.B., V.L.); Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, Texas (A.C., M.-J.T.); Molecular Oncology Group, McGill University Health Centre, Montréal, Québec, Canada (V.G.); Department of Physiology, University of California, San Francisco, San Francisco, California (H.I.); Division of Endocrinology, Diabetes, and Metabolism, Institute for Diabetes, Obesity, and Metabolism, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania (M.L.); Institute for Molecular Bioscience, The University of Queensland, St. Lucia, Queensland, Australia (G.M.); Ludwig Institute for Cancer Research, Department of Cell and Molecular Biology, Karolinska Institutet, Stockholm, Sweden (T.P.); AliX, Illkirch, France (J.-P.R.); Medical Research Council Laboratory of Molecular Biology, Cambridge, United Kingdom (J.S.); and Department of Cell Biology and Neuroscience, University of California, Riverside, California (F.S.)
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Vincent Laudet
Structure and Evolution of Nuclear Hormone Receptors, Unité Mixte de Recherche 5161 du Centre National de la Recherche Scientifique, Institut National de la Recherche Agronomique 1237, Laboratoire de Biologie Moléculaire de la Cellule, Institut Fédératif de Recherche 128 BioSciences Lyon-Gerland, Ecole Normale Supérieure de Lyon, Lyon, France (G.B., V.L.); Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, Texas (A.C., M.-J.T.); Molecular Oncology Group, McGill University Health Centre, Montréal, Québec, Canada (V.G.); Department of Physiology, University of California, San Francisco, San Francisco, California (H.I.); Division of Endocrinology, Diabetes, and Metabolism, Institute for Diabetes, Obesity, and Metabolism, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania (M.L.); Institute for Molecular Bioscience, The University of Queensland, St. Lucia, Queensland, Australia (G.M.); Ludwig Institute for Cancer Research, Department of Cell and Molecular Biology, Karolinska Institutet, Stockholm, Sweden (T.P.); AliX, Illkirch, France (J.-P.R.); Medical Research Council Laboratory of Molecular Biology, Cambridge, United Kingdom (J.S.); and Department of Cell Biology and Neuroscience, University of California, Riverside, California (F.S.)
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Abstract

Half of the members of the nuclear receptors superfamily are so-called “orphan” receptors because the identity of their ligand, if any, is unknown. Because of their important biological roles, the study of orphan receptors has attracted much attention recently and has resulted in rapid advances that have helped in the discovery of novel signaling pathways. In this review we present the main features of orphan receptors, discuss the structure of their ligand-binding domains and their biological functions. The paradoxical existence of a pharmacology of orphan receptors, a rapidly growing and innovative field, is highlighted.

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Pharmacological Reviews: 58 (4)
Pharmacological Reviews
Vol. 58, Issue 4
1 Dec 2006
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Research ArticleSpecial Issue IUPHAR Compendium of the Pharmacology and Classification of the Nuclear Receptor Superfamily 2006

International Union of Pharmacology. LXVI. Orphan Nuclear Receptors

Gérard Benoit, Austin Cooney, Vincent Giguere, Holly Ingraham, Mitch Lazar, George Muscat, Thomas Perlmann, Jean-Paul Renaud, John Schwabe, Frances Sladek, Ming-Jer Tsai and Vincent Laudet
Pharmacological Reviews December 1, 2006, 58 (4) 798-836; DOI: https://doi.org/10.1124/pr.58.4.10

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Research ArticleSpecial Issue IUPHAR Compendium of the Pharmacology and Classification of the Nuclear Receptor Superfamily 2006

International Union of Pharmacology. LXVI. Orphan Nuclear Receptors

Gérard Benoit, Austin Cooney, Vincent Giguere, Holly Ingraham, Mitch Lazar, George Muscat, Thomas Perlmann, Jean-Paul Renaud, John Schwabe, Frances Sladek, Ming-Jer Tsai and Vincent Laudet
Pharmacological Reviews December 1, 2006, 58 (4) 798-836; DOI: https://doi.org/10.1124/pr.58.4.10
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    • Introduction
    • What Are Orphan Receptors?
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    • Unorthodox LBD for Unorthodox NRs
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